The Drug Abuse Research Center brings together four laboratory groups employing different approaches to the neurobiological bases for actions of drugs of abuse. Multidisciplinary approaches in the laboratories include biochemistry, molecular biology, neuroanatomy and neurophysiology with substantial technical and conceptual coordination and collaboration between groups. The common thematic focus, as in past periods of support, is The Dynamics of Signaling by Molecular Messengers Relevant to Actions of Drugs of Abuse. Snyder will explore three areas of signal transduction with a special focus on neurotoxicity (1) nitric oxide synthase associated proteins (2) heme oxygenase products: CO and bilirubin (3) glyceraldehydes-3-phosphate dehydrogenase and cell death. The Dawsons will identify and characterize genes dependent on signaling by calcium and NMDA receptor transmission. Worley will deal with the function and regulation of immediate early genes that are dynamically regulated by cocaine with a special emphasis on Rheb, a novel member of the Ras signaling pathway. Baraban will focus on two aspects of intraneuronal signaling linked to neuronal plasticity and drug abuse. One is Tech, a guanine nucleotide exchange factor for Rho family members, that is selectively expressed in neurons. The other is Translin, a component of RNA binding complexes that have been implicated in dentritic RNA processing.